Bone is a highly dynamic tissue characterized by continuous formation and readsorption. An imbalance in formation and readsorption can be implicated in metabolic bone diseases such as osteopetrosis and osteoporosis.
Bone formation and readsorption is mediated at least in part by osteoblasts and osteoclasts. These cells exert opposite effects on bone growth. Osteoblasts secrete molecules that form the organic matrix of bone, while osteoclasts promote dissolution of the bone matrix and solubilization of bone salts. Net bone tissue formation occurs when the rate of bone deposition exceeds the rate of bone resorption, while bone loss occurs when the rate of resorption exceeds deposition. Increased breakdown of bone, as is observed in diseases such as osteoporosis, can lead to reduced bone mass and strength, as well as an increased risk of fractures, and slow or incomplete repair of broken bones.
Osteoclasts are thought to form from hematopoietic precursor cells in the bone marrow. Early development of bone marrow precursor cells to preosteoclasts are believed to mediated by soluble factors such as tumor necrosis factor-alpha. (TNF-alpha), tumor necrosis factor-beta (TNF-beta), interleukin-1 (IL-1), interleukin-4 (IL-4), interleukin-6 (IL-6), and leukemia inhibitory factor (LIF).
One protein involved in bone metabolism is osteoprotegerin (OPG), which is also known as osteoclastogenesis inhibitory factor (OCIF). OPG includes two polypeptide domains having different structural and functional properties. It has cytokine-like activities and is a member of the tumor necrosis factor (TNF) receptor superfamily. OPG has been reported to act as a soluble factor in the regulation of bone mass by negatively regulating osteoclast formation in vitro and in vivo. By inhibiting osteoclast formation, OPG is thought to promote net bone growth. Transgenic mice expressing the OPG polypeptide show increased bone density and lowered amounts of bone loss.
OPG-deficient mice also exhibit medial calcification of the aorta and renal arteries, suggesting that regulation of OPG, its signaling pathway, or its ligand(s) may play a role in the long-observed association between osteoporosis and vascular calcification.